Advertisement

Crystallography Reports

, Volume 64, Issue 1, pp 98–104 | Cite as

Molecular Dynamics Study of Thymidine Phosphorylase from E. coli in the Apo Form and in Complexes with Substrates

  • D. D. Sidorov-Biryukov
  • D. D. Podshivalov
  • V. I. Timofeev
  • N. E. Zhukhlistova
  • I. P. KuranovaEmail author
STRUCTURE OF MACROMOLECULAR COMPOUNDS

Abstract

Models of E. coli thymidine phosphorylase in complexes with the substrates — the complex with phosphate and the complex with phosphate and thymidine — were obtained by molecular docking calculations. The influence of the substrates on domain movements in the dimeric thymidine phosphorylase molecule was probed by molecular dynamics simulations. The two subunits were shown to function asynchronously. In the thymidine phosphorylase/phosphate and thymidine phosphorylase/phosphate/thymidine complexes, phosphate is more weakly bound in the active site and moves away from the phosphate-binding site during the 60-ns trajectory, whereas thymidine remains in the active site but undergoes conformational changes.

Notes

ACKNOWLEDGMENTS

This work was supported by the Ministry of Science and Higher Education within the State assignment FSRC “Crystallography and Photonics” RAS.

REFERENCES

  1. 1.
    M. J. Pugmire and S. E. Ealick, Biochem. J. 361, 1 (2002).CrossRefGoogle Scholar
  2. 2.
    M. Ligo, K. Nishikata, Y. Nakajiama, et al., Biochem. Pharmacol. 39 (7), 1247 (1990).CrossRefGoogle Scholar
  3. 3.
    A. Yoshimura, Y. Kuwazuru, T. Furukawa, et al., Biochim. Biophys. Acta 1034, 107 (1990).CrossRefGoogle Scholar
  4. 4.
    K. Usuki, J. Saras, J. Waltenberger, et al., Biochem. Biophys. Res. Commun. 184, 1311 (1992).CrossRefGoogle Scholar
  5. 5.
    S. Akiyama, T. Furukawa, T. Sumizawa, et al., Cancer Sci. 95 (11), 851 (2004).CrossRefGoogle Scholar
  6. 6.
    E. L. Schwartz, N. Baptiste, S. Megati, et al., Cancer Res. 55, 3543 (1995).Google Scholar
  7. 7.
    M. R. Walter, W. J. Cook, L. B. Cole, et al., J. Biol. Chem. 265, 14016 (1990).Google Scholar
  8. 8.
    M. J. Pugmire, W. J. Cook, A. Jasanoff, et al., J. Mol. Biol. 281, 285 (1998).CrossRefGoogle Scholar
  9. 9.
    V. I. Timofeev, Yu. A. Abramchik, I. V. Fateev, et al., Crystallogr. Rep. 58 (6), 842 (2013).ADSCrossRefGoogle Scholar
  10. 10.
    M. J. Pugmire and S. E. Ealick, Structure 6, 1467 (1998).CrossRefGoogle Scholar
  11. 11.
    R. A. Norman, S. T. Barry, M. Bate, et al., Structure 12, 75 (2004).CrossRefGoogle Scholar
  12. 12.
    Omari. K. El, A. Bronckaers, S. Liekens, et al., Biochem. J. 399, 199 (2006).Google Scholar
  13. 13.
    M. J. Pugmire and S. E. Ealick, Biochem. J. 361, 1 (2002).CrossRefGoogle Scholar
  14. 14.
    S. W. Rick, Y. G. Abashkin, R. L. Hilderbrandt, and S. K. Burt, PROTEINS: Struct., Funct., Genet. 37, 242 (1999).CrossRefGoogle Scholar
  15. 15.
    O. Trott and A. J. Olson, J. Comput. Chem. 31, 455 (2010).Google Scholar
  16. 16.
    V. Timofeev, Yu. Abramchik, N. Zhukhlistova, et al., Acta Crystallogr. D 70, 1155 (2014).CrossRefGoogle Scholar
  17. 17.
    I. Soteras Gutierrez, F.-Y. Lin, K. Vanommeslaeghe, et al., Bioorg. Med. Chem. (2016).Google Scholar
  18. 18.
    W. L. Jorgensen, J. Chandrasekhar, J. D. Madura, et al., J. Chem. Phys. 79, 926 (1983).ADSCrossRefGoogle Scholar
  19. 19.
    H. J. C. Berendsen, J. P. M. Postma, Gunsteren. W. F. van, et al., J. Chem. Phys. 81 (8), 3684 (1984). Bibcode:1984JChPh..81.3684B.  https://doi.org/10.1063/1.448118
  20. 20.
    M. Parrinello and A. Rahman, J. Chem. Phys. 76 (5), 2662 (1982).ADSCrossRefGoogle Scholar
  21. 21.
    J. Mendieta, S. Martín-Santamaría, E.-M. Priego, et al., Biochemistry 43 (2), 409 (2004).CrossRefGoogle Scholar
  22. 22.
    N. G. Panova, K. S. Alekseev, A. S. Kuz’michev, et al., Biokhimiya 72 (1), 27 (2007).Google Scholar
  23. 23.
    N. Burton, M. Harrison, J. Hart, et al., Faraday Discuss. 110, 463 (1998).ADSCrossRefGoogle Scholar

Copyright information

© Pleiades Publishing, Inc. 2018

Authors and Affiliations

  • D. D. Sidorov-Biryukov
    • 1
  • D. D. Podshivalov
    • 1
    • 2
    • 3
  • V. I. Timofeev
    • 1
    • 2
  • N. E. Zhukhlistova
    • 1
  • I. P. Kuranova
    • 1
    • 2
    Email author
  1. 1.Shubnikov Institute of Crystallography of Federal Scientific Research Centre “Crystallography and Photonics”, Russian Academy of SciencesMoscowRussia
  2. 2.National Research Centre “Kurchatov Institute”MoscowRussia
  3. 3.M. V. Lomonosov Moscow State UniversityMoscowRussia

Personalised recommendations